Relationship of prediagnostic body mass index with survival after colorectal cancer: Stage‐specific associations

Higher body mass index (BMI) is a well‐established risk factor for colorectal cancer (CRC), but is inconsistently associated with CRC survival. In 6 prospective studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), 2,249 non‐Hispanic white CRC cases were followed for a median 4.5 years after diagnosis, during which 777 died, 554 from CRC‐related causes. Associations between prediagnosis BMI and survival (overall and CRC‐specific) were evaluated using Cox regression models adjusted for age at diagnosis, sex, study and smoking status (current/former/never). The association between BMI category and CRC survival varied by cancer stage at diagnosis (I‐IV) for both all‐cause (p‐interaction = 0.03) and CRC‐specific mortality (p‐interaction = 0.04). Compared to normal BMI (18.5–24.9 kg/m²), overweight (BMI 25.0–29.9) was associated with increased mortality among those with Stage I disease, and decreased mortality among those with Stages II–IV disease. Similarly, obesity (BMI ≥30) was associated with increased mortality among those with Stages I–II disease, and decreased mortality among those with Stages III–IV disease. These results suggest the relationship between BMI and survival after CRC diagnosis differs by stage at diagnosis, and may emphasize the importance of adequate metabolic reserves for colorectal cancer survival in patients with late‐stage disease.     

Prediagnostic body weight and survival in high grade glioma

Greater adiposity has been linked to an increased risk and/or poorer survival in a variety of cancers. We examined whether prediagnostic body weight 1–5 years prior to diagnosis is associated with survival in patients with high grade glioma. The analysis was based on a series of patients with high-grade glioma (N = 853) enrolled in a US-based multicenter case–control study. Subjects reported height and weight 1–5 years prior to interview and at age 21. BMI was categorized according to WHO criteria as underweight (BMI <18.5 kg/m²), normal weight (BMI 18.5–24.9 kg/m²), overweight (BMI 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²). Proportional hazards regression was used to estimate hazard ratios (HR) and 95 % confidence intervals (CIs) for glioma-related death according to body mass index (BMI, kg/m²). Overall survival was reduced among patients underweight (median survival: 12.0 months) or obese (median: 13.6 months) when compared to patients of normal weight (median: 17.5 months) prior to glioma diagnosis (p = 0.004). In a multivariate model controlling for other prognostic factors, an excess mortality was observed in patients reporting obese body weights 1–5 years prior to study interview when compared to patients with a normal BMI (HR = 1.32; 95 % CI 1.04–1.68). Consistent patterns of association with excess body weight were observed in men and women, and all findings were similar regardless of treatment for glioma. A lower than optimal body weight was associated with a nonsignificant excess mortality in multivariate analysis. Premorbid obesity was significantly associated with a poor patient outcome independent of treatment and established prognostic factors. Excess body weight may be an adverse prognostic factor in glioma, a relationship observed across a spectrum of cancer types. The current findings linking prediagnostic body weight with mortality in high-grade glioma warrant further research.     

The ‘obesity paradox’ and survival after colorectal cancer: true or false?

Body mass index (BMI), as an approximation of general adiposity, is an established risk factor for incidence of several adult cancer types, including colorectal cancer (CRC). There is a common perception that these relationships extrapolate directly as adverse prognostic factors after diagnosis, but evidence for this is lacking. The paper from Sclesinger et al. in this issue of the journal adds a new dimension to this debate focusing on relationships of post-diagnosis BMI (as a marker of the steady-state weight among survivors) and survival, and provides evidence on a decreased mortality risk among overweight (post-diagnosis BMI 25.0–29.9 kg/m²) compared with normal weight (post-diagnosis BMI 18.5–24.9 kg/m²) CRC survivors—an example of an ‘obesity paradox.’ The observation of the ‘obesity paradox’ is well documented in the methodology literature, but perhaps, less familiar to the cancer readership. Three broad classes of explanation are posited: (1) the associations are true and plausible; (2) the associations are false and reflect methodological issues; or (3) the observations represent a specific form of selection bias, known as collider bias. The present author argues that the obesity paradox reflects the latter—a product of a statistical bias—and emphasizes that, while these findings are hypothesis generating, they will not alter clinical practice or recommendations.     

Survival impact of postoperative body mass index in gastric cancer patients undergoing gastrectomy

BackgroundThe relationship between preoperative body mass index (BMI) and the survival of postoperative gastric cancer patients is not clear. Furthermore, the survival impact with postoperative BMI is not known, even though weight loss is inevitable after gastrectomy.MethodsPatients who underwent gastrectomy for gastric cancer between 2000 and 2008 were included in the study (n = 1909). Patients were divided into three groups based on their BMIs: low (<18.5 kg/m²), normal (18.5–24.9 kg/m²), and high BMI (≥25.0 kg/m²). Patient survival was compared according to BMI at two time points: baseline and 1 year after surgery.ResultsRegarding BMI 1 year after surgery, overall survival, disease-specific survival, and recurrence-free survival were longer in the high BMI group than the low and normal BMI groups. In a Cox proportional hazards model, adjusting for the patient's age, sex, type of surgery, tumour stage, histology, curative resection, and BMI at baseline, a high BMI 1 year after surgery was associated with lower overall mortality compared to normal BMI (hazard ratio 0.51; 95% confidence interval, 0.26–0.98). However, BMI at baseline was not an independent prognostic factor.ConclusionBMI 1 year after surgery significantly predicted the long-term survival of patients with gastric cancer compared with the preoperative BMI.     

Overall and abdominal obesity and prostate cancer risk in a West African population: An analysis of the Ghana Prostate Study

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m² for cases and 24.3 kg/m² for controls. After adjustment, men with BMI ≥ 30 kg/m² had an increased risk of prostate cancer relative to men with BMI < 25 kg/m² (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region.     

Body mass index and survival in patients with renal cell carcinoma: A clinical‐based cohort and meta‐analysis

Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, we analyzed a large cohort of patients with RCC and undertook a meta‐analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow‐up through 2008. Patients were grouped according to BMI (kg/m²): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese ≥25. We estimated survival using the Kaplan–Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer‐specific survival (CSS) with adjustment for covariates. We performed a meta‐analysis of BMI and OS, CSS and recurrence‐free survival (RFS) from all relevant studies using a random‐effects model. The 5‐year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45; 95% CI: 0.29–0.68) and CSS (HR = 0.47; 95% CI: 0.29–0.77] in obese patients than in normal weight patients. The meta‐analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43–0.76), CSS (HR = 0.59; 95% CI: 0.48–0.74) and RFS (HR = 0.49; 95% CI: 0.30–0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.     

Body mass index and mortality in patients with gastric cancer: a large cohort study

Background

The effects of obesity on prognosis in gastric cancer are controversial.

Aims

To evaluate the association between body mass index (BMI) and mortality in patients with gastric cancer.

Methods

A single-institution cohort of 7765 patients with gastric cancer undergoing curative gastrectomy between October 2000 and June 2016 was categorized into six groups based on BMI: underweight (<?18.5 kg/m²), normal (18.5 to?<?23 kg/m²), overweight (23 to?<?25 kg/m²), mildly obese (25 to?<?28 kg/m²), moderately obese (28 to?<?30 kg/m²), and severely obese (≥?30 kg/m²). Hazard ratios (HRs) for overall survival (OS) and disease-specific survival (DSS) were calculated using Cox proportional hazard models.

Results

We identified 1279 (16.5%) all-cause and 763 (9.8%) disease-specific deaths among 7765 patients over 83.05 months (range 1.02–186.97) median follow-up. In multivariable analyses adjusted for statistically significant clinicopathological characteristics, preoperative BMI was associated with OS in a non-linear pattern. Compared with normal-weight patients, underweight patients had worse OS [HR 1.42; 95% confidence interval (CI) 1.15–1.77], whereas overweight (HR 0.84; 95% CI 0.73–0.97), mildly obese (HR 0.77; 95% CI 0.66–0.90), and moderately obese (HR 0.77; 95% CI 0.59–1.01) patients had better OS. DSS exhibited a similar pattern, with lowest mortality in moderately obese patients (HR 0.58; 95% CI 0.39–0.85). Spline analysis showed the lowest all-cause mortality risk at a BMI of 26.67 kg/m².

Conclusion

In patients undergoing curative gastric cancer surgery, those who were overweight or mildly-to-moderately obese (BMI 23 to?<?30 kg/m²) preoperatively had better OS and DSS than normal-weight patients.

     

Central adiposity,obesity during early adulthood,and pancreatic cancer mortality in a pooled analysis of cohort studies

BackgroundBody mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk.DesignWe conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18–21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models.ResultsHigher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m²), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m², HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m², HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m², HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m²). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m²).ConclusionsOur results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.     

Body Mass Index (BMI), BMI Change,and Overall Survival in Patients With SCLC and NSCLC: A Pooled Analysis of the International Lung Cancer Consortium

IntroductionThe relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied.MethodsIndividual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots.ResultsOverall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m²; aHR = 1.56; 95% confidence interval [CI]:1.43–1.70) or morbidly overweight (BMI > 40 kg/m²; aHR = 1.09; 95% CI: 0.95–1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m² ≤ BMI < 30 kg/m²; aHR = 0.89; 95% CI: 0.85–0.95) or obese (30 kg/m² ≤ BMI ≤ 40 kg/m²; aHR = 0.86; 95% CI: 0.82–0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2–1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0–1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets.ConclusionsBoth being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.     

The effects of body mass index on complications and survival outcomes in patients with cervical carcinoma undergoing curative chemoradiation therapy

BACKGROUND:

The effect of body mass index (BMI) on treatment outcomes for patients with locally advanced cervical carcinoma who receive definitive chemoradiation is unclear.

METHODS:

The cohort in this study included all patients with cervical carcinoma (n = 404) who had stage IB₁ disease and positive lymph nodes or stage ≥IB₂ disease and received treatment at the authors' facility between January 1998 and January 2008. The mean follow‐up was 47.2 months. BMI was calculated using the National Institute of Health online calculator. BMI categories were created according to the World Health Organization classification system. Primary outcomes were overall survival, disease‐free survival, and complication rate. Univariate and multivariate analyses were performed. Kaplan‐Meier survival curves were generated and compared using Cox proportional hazard models.

RESULTS:

On multivariate analysis, compared with normal weight (BMI 18.5‐24.9 kg/m²), a BMI <18.5 kg/m² was associated with decreased overall survival (hazard ratio, 2.37; 95% confidence interval, 1.28‐4.38; P < .01). The 5‐year overall survival rate was 33%, 60%, and 68% for a of BMI <18.5 kg/m², a BMI from 18.5 kg/m² to 24.9 kg/m², and a BMI >24.9 kg/m², respectively. A BMI <18.5 kg/m² was associated with increased risk of grade 3 or 4 complications compared with a BMI >24.9 kg/m² (radiation enteritis: 16.7% vs 13.6%, respectively; P = .03; fistula: 11.1% vs 8.8%, respectively; P = .05; bowel obstruction: 33.3% vs 4.4%, respectively; P < .001; lymphedema: 5.6% vs 1.2%, respectively; P = .02).

CONCLUSIONS:

Underweight patients (BMI <18.5 kg/m²) with locally advanced cervical cancer had diminished overall survival and more complications than normal weight and obese patients. Cancer 2011. © 2010 American Cancer Society.     

Prospective cohort study of general and central obesity,weight change trajectory and risk of major cancers among Chinese women

General obesity, typically measured using body mass index (BMI), has been associated with an increased risk of several cancers. However, few prospective studies have been conducted in Asian populations. Although central obesity, often measured using waist–hip ratio (WHR), is more predictive for type 2 diabetes and cardiovascular diseases (CVD) risk than BMI, knowledge of its association with cancer incidence is limited. In a cohort of 68,253 eligible Chinese women, we prospectively investigated the association of BMI, WHR and weight change during adulthood with risk of overall cancer and major site‐specific cancers using multivariate Cox proportional hazard models. Compared to the BMI group of 18.5–22.9 kg/m², obese (BMI ≥ 30 kg/m²) women were at an increased risk of developing overall cancer (hazard ratio = 1.36, 95% confidence interval = 1.21–1.52), postmenopausal breast cancer (HR: 2.43, 95% CI: 1.73–3.40), endometrial cancer (HR: 5.34, 95% CI: 3.48–8.18), liver cancer (HR: 1.93, 95% CI: 1.14–3.27) and epithelial ovarian cancer (HR: 2.44, 95% CI: 1.37–4.35). Weight gain during adulthood (per 5 kg gain) was associated with increased risk of all cancers combined (HR: 1.05, 95% CI: 1.03–1.08), postmenopausal breast cancer (HR: 1.17, 95% CI: 1.10–1.24) and endometrial cancer (HR: 1.37, 95% CI: 1.27–1.48). On the other hand, WHR was not associated with cancer risk after adjustment for baseline BMI. These findings suggest that obesity may be associated with cancer risk through different mechanisms from those for type 2 diabetes and CVD and support measures of maintaining health body weight to reduce cancer risk in Chinese women.     

The association between body mass index and postoperative complications, 30-day mortality and long-term survival in Dutch patients with colorectal cancer

IntroductionThis retrospective study aims to examine the association between body mass index (BMI) and serious postoperative complications, 30-day mortality and overall survival in colorectal cancer (CRC) patients.Materials and methodsAll CRC patients diagnosed between 2008 and 2013 in the south-eastern part of the Netherlands were included. Patients were categorized into four BMI groups: underweight (<18.5), normal weight (18.5 ≥ BMI<25), overweight (25 ≥ BMI<30), and obese (≥30).ResultsA total of 7371 CRC patients were included (underweight 133 (1.8%); normal weight 2054 (41.4%); overweight 2955 (40.1%); obesity 1229 (16.7%)). Underweight patients were more likely to have postoperative complications (18.8% vs. 11.7%, adjusted OR 1.95, 95% CI 1.08–3.49) and had a worse 30-day mortality (9.8% vs. 3.3%, adjusted OR 4.37, 95% CI 2.03–9.42) compared to normal weight patients. After stratification for stage (stage I-III and stage IV), underweight was associated with a worse overall survival in both groups compared to normal weight (stage I-III: HR 2.06, 95%CI 1.51–2.80; stage IV: HR 1.65, 95% CI 1.11–2.45). Overweight was associated with an improved overall survival compared to normal weight in both stage groups. Only in stage IV patients obesity was associated with a significant better overall survival compared to stage IV normal weight patients.ConclusionUnderweight CRC patients were more likely to have postoperative complications and a worse 30-day mortality compared to patients in other BMI categories. The underweight population also has a worse long-term survival while overweight CRC patients and obese stage IV CRC patients were associated with an improved survival compared to normal weight patients.     

Role of BMI and age in predicting pathologic vertebral fractures in newly diagnosed multiple myeloma patients: A retrospective cohort study

Vertebral fractures affect approximately 30% of myeloma patients and lead to a poor impact on survival and life quality. In general, age and body mass index (BMI) are reported to have an important role in vertebral fractures. However, the triangle relationship among age, BMI, and vertebral fractures is still unclear in newly diagnosed multiple myeloma (NDMM) patients. This study recruited consecutive 394 patients with NDMM at Taipei Veterans General Hospital between January 1, 2005 and December 31, 2015. Risk factors for vertebral fractures in NDMM patients were collected and analyzed. The survival curves were demonstrated using Kaplan‐Meier estimate. In total, 301 (76.4%) NDMM patients were enrolled in the cohort. In the median follow‐up period of 18.0 months, the median survival duration in those with vertebral fractures ≥ 2 was shorter than those with vertebral fracture < 2 (59.3 vs 28.6 months; P = 0.017). In multivariate Poisson regression, BMI < 18.5 kg/m² declared increased vertebral fractures compared with BMI ≥ 24.0 kg/m² (adjusted RR, 2.79; 95% CI, 1.44–5.43). In multivariable logistic regression, BMI < 18.5 kg/m² was an independent risk factor for vertebral fractures ≥ 2 compared with BMI ≥ 24.0 kg/m² (adjusted OR, 6.05; 95% CI, 2.43–15.08). Among age stratifications, patients with both old age and low BMI were at a greater risk suffering from increased vertebral fractures, especially in patients > 75 years and BMI < 18.5 kg/m² (adjusted RR, 12.22; 95% CI, 3.02–49.40). This is the first study that demonstrated that age had a significant impact on vertebral fractures in NDMM patients with low BMI. Elder patients with low BMI should consider to routinely receive spinal radiographic examinations and regular follow‐up.     

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B‐cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B‐cell lymphoma patients treated with R‐CHOP or R‐CHOP–like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m²), 58 (14.3%); normal weight (≥18.5 to <25 kg/m²), 262 (64.5%); overweight (≥25 to <30 kg/m²), 75 (18.5%); and obese (≥30.0 kg/m²), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5‐y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m²) had significantly inferior OS than those with a high BMI (≥25 kg/m²) (5‐y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5‐y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.     

Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies

BackgroundPositive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised.MethodsWe systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations.ResultsEighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29–1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02–1.12) for overweight (BMI 25.0–<30.0) and 1.10 (95% CI 0.92–1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26–2.41) for pre-menopausal and 1.34 (95% CI 1.18–1.53) for post-menopausal breast cancer. For each 5 kg/m² increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively.ConclusionsObesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.     

Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy

Purpose

Obesity is associated with an increased risk of development and recurrence of colorectal cancer. However, the role of obesity in advanced colorectal cancer (ACC) patients is unknown. We investigated the effect of body mass index (BMI) on overall survival (OS) in ACC patients receiving systemic treatment in two large phase III studies (CAIRO and CAIRO2).

Patients and methods

Treatment data were obtained and analysed from 796 ACC patients who were treated with chemotherapy in the CAIRO study, and from 730 ACC patients who were treated with chemotherapy plus targeted therapy in the CAIRO2 study. Baseline height and weight were used to assign patients to one of the following BMI categories: A (<18.5 kg/m²), B (18.5-24.9 kg/m²), C (25.0-29.9 kg/m²) and D (?30.0 kg/m²).

Results

In 796 patients of the CAIRO study a high BMI was associated with better median OS (8.0, 14.9, 18.4 and 19.5 months for BMI categories A, B, C, and D, respectively; P = 0.001), and was an independent prognostic factor for OS in a multivariate analysis. BMI was not associated with OS in 730 patients who participated in the CAIRO2 study, although a trend was observed.

Conclusions

These results show that BMI is an independent prognostic factor for survival in patients receiving chemotherapy, but not in patients receiving chemotherapy and targeted therapy. The possible decreased efficacy of bevacizumab in obese patients may explain this discrepant result. The role of BMI in patients receiving targeted therapy should be further tested.     

The U-shaped association between body mass index and gastric cancer risk in the Helicobacter pylori Biomarker Cohort Consortium: A nested case–control study from eight East Asian cohort studies

The association between body mass index (BMI) and noncardia gastric cancer (NCGC) risk remains controversial. The purpose of our study was to examine the association of BMI with NCGC risk with consideration of Helicobacter pylori (HP) biomarkers. This international nested case–control study, composed of 1,591 incident NCGC cases and 1,953 matched controls, was established from eight cohorts in China, Japan and Korea, where the majority of NCGCs are diagnosed worldwide. HP antibody biomarkers were measured in blood collected at cohort enrollment by multiplex serology. The NCGC risk according to baseline BMI was estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CIs). We found a U-shaped association between BMI category and NCGC risk. Compared to those with reference BMI (22.6–25.0 kg/m²), those with lower and higher BMI had an increased NCGC risk (BMI <18.5 kg/m², OR = 1.56, 95% CI = 1.04–2.34; BMI >27.5 kg/m², OR = 1.48, 95% CI = 1.15–1.91; adjusted for age, sex and smoking). The U-shaped association was persistent among subjects with HP infection and high-risk biomarkers (HP+ CagA+: BMI <18.5 kg/m², OR = 1.60, 95% CI = 1.00–2.55; BMI >27.5 kg/m², OR = 1.59, 95% CI = 1.21–2.11; and Omp+ HP0305+: BMI <18.5 kg/m², OR = 1.88, 95% CI = 1.04–3.42; BMI >27.5 kg/m², OR = 1.70, 95% CI = 1.20–2.42, respectively). Our study provides evidence of significantly increased NCGC risk among individuals with low or high BMI, including in subjects with high-risk HP biomarkers (HP+ CagA+, Omp+ HP0305+) in the high-risk area of East Asia.     

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16‐ to 19‐year‐old Israeli males. 1,382,093 Jewish Israeli males aged 16–19 who underwent anthropometric measurements, a general intelligence test (GIT) and other examinations during 1967–2011, were followed up to December 31, 2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age‐specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person‐years of follow‐up, 97 were included in multivariable analyses. Compared to “healthy” BMI (18.5–24.9 kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence interval [CI] 1.14–3.55, p = 0.015) in overweight (25.0 ≤ BMI < 30.0 kg/m²) adolescents; and HR = 4.97 (95%CI 2.14–11.53, p = 0.0002) in obese (BMI ≥ 30.0 kg/m²) adolescents. When CDC age‐specific BMI percentiles were assessed results were similar and statistically significant for obesity. In addition, low (vs. high) GIT score (HR = 4.76, 95%CI 1.96–12.50, p = 0.001) and European (vs. west‐Asian) origin (HR = 1.99, 95%CI 1.19–3.34, p = 0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored.     

Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women

Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model‐insulin resistance (HOMA‐IR—a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross‐classified by BMI (18.5–<25.0, 25.0–<30.0 and ≥30.0 kg/m²) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA‐IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.     

Progesterone receptor status modifies the association between body mass index and prognosis in women diagnosed with estrogen receptor positive breast cancer

The role of progesterone receptor (PR) status on the association between obesity and prognosis of estrogen receptor positive (ER+) breast cancer (BC) remains poorly understood. We aim to examine whether this association varies according to the tumor PR status. Data for 3,747 women diagnosed with nonmetastatic ER+ invasive BC between 1995 and 2010 were analyzed. Women were classified according to their body mass index (BMI) (<18.5, 18.5–24.9, 25.0–29.9 or ≥30.0 kg/m²). Tumor PR status (PR−, PR+) was evaluated by immunohistochemistry. Hazard ratios (HR) for survival outcomes were estimated using multivariable Cox regression models. Effect modification was assessed on both additive and multiplicative scales using relative excess risk due to interaction and ratio of HRs, respectively. After a median follow-up of 5.9 years (range: 3.4–9.2), women with PR− tumors and underweight (HR = 2.76, 95% CI: 1.40–4.91), overweight (HR = 2.02, 95% CI: 1.43–2.81) or obese (HR = 2.51, 95% CI: 1.67–3.65) had increased risk of all-cause mortality, when compared to normal weight women with PR+ tumors. A similar pattern of associations was observed for BC-specific mortality. In contrast, women with PR+ tumors had similar risks for both mortality outcomes, regardless of BMI. On the additive scale, all-cause mortality was modified by PR status for overweight and obese women, whereas for BC-specific mortality, it was only modified for underweight women. The same observations were found on the multiplicative scale. These results suggest that poorer survival associated with low and high BMI among women diagnosed with ER+ BC may depend on the tumor PR status.